NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 (R&R) forms and the Grants.gov SBIR/STTR Application Guide. APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and should be started at least two weeks in advance of the planned submission. See Section IV.

Two steps are required for on time submission:

1) The application must be submitted to Grants.gov by the submission date (see “Key Dates” below)

2) Applicants must complete a verification step in the eRA Commons within two business days of notification from NIH. Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check the Commons.

The participating institutes of the National Institutes of Health invite the small business community to apply cutting edge-technology to develop new approaches and chemical modifications that will increase the long term stability, delivery and targeting of siRNAs in cells and tissues for laboratory and therapeutic applications.

The number of awards made under this solicitation will depend on the overall scientific merit of the applications and the availability of funds.

This PA uses the STTR (R41/R42) mechanisms.

This funding opportunity will utilize the Small Business Technology Transfer (STTR) mechanism, but will be run in parallel with a program announcement of identical scientific scope (PA-06-003) that will utilize the Small Business Innovation Research (SBIR) grant mechanism.

Only United States SBCs are eligible to submit SBIR applications. A SBC is one that, on the date of award for both Phase I and Phase II funding agreements, meets ALL of the criteria as described inSection III. I.A.

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. On an SBIR application, the Project Director/Principal Investigator (PD/PI) must have his/her primary employment (more than 50%) with the SBC at the time of award and for the duration of the project.

Applicant SBCs may submit more than one application, provided each application is scientifically distinct.

Gene silencing by RNA interference (RNAi) takes advantage of an endogenous defense mechanism of protecting cells from invading viruses and from damage by transposable genetic elements. Since the description of the phenomenon in 1995, and unraveling of its mechanism in 1998, RNAi has emerged as a powerful strategy for silencing genes and has become a widely used tool due to its great simplicity and high efficiency. RNAi is induced by dsRNA which when introduced intracellularly is processed by an enzyme known as Dicer. This enzyme cleaves the dsRNA into 21-23 nt RNA fragments (siRNA for short-interfering RNA) which are then incorporated into protein complexes known as RNA-induced silencing complexes (RISC). The RISC recognizes and cleaves cognate mRNAs which results in the degradation of the targeted transcript.

The possible therapeutic applications of RNAi are broad and far reaching, ranging from acquired diseases, such as viral infections, to genetic disorders, particularly where there is a dominant gain-in-function mutation. Promising results in gene silencing have already been shown either in vitro or in vivo for viral diseases (such as HIV/AIDS, influenza, human papillomavirus infection, various hepatitis strains, smallpox, and SARS), neurodegenerative diseases (such as Parkinson's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, and Alzheimer's disease), cancer, inflammatory diseases (such as rheumatoid arthritis), and autoimmune diseases (such as type 1 diabetes mellitus). RNAi approaches also hold promise for new insights into heart, lung, and blood diseases. Preliminary studies suggest beneficial effects in improving stroke therapy as well as in helping dilated cardiomyopathy patients through enhanced survival of myocardial endothelial cells. RNAi approaches also offer to overcome the thrombotic effects of antibodies in countering acute or chronic inflammatory states. Similar approaches for therapeutic approaches are being tested for asthma and pulmonary hypertension. The intense interest in RNAi has come at least in part because of its potential broad therapeutic applicability across such a wide spectrum of disorders and to the fact that RNAi takes advantage of a natural cellular process. The discovery of RNAi has revolutionized genetic research, and is on the verge of spawning an entirely new class of drugs to treat human genetic diseases, provided that significant barriers in delivery and targeting can be overcome. RNAi is also amenable for recessively inherited diseases or for polygenic disorders (such as Parkinson's or Alzheimer's disease). In these cases, knowledge of molecular pathways may provide alternative targets for RNAi where, for example, suppression of a key downstream target normally inhibited by the protein product of the diseased allele could have therapeutic potential.

The need to combine high specificity with high potency is important to the continued development of siRNA in research and therapy development. This PA will focus on techniques and technologies leading to improved chemical synthesis and delivery of RNAi, particularly those incorporating chemical modifications that change the properties of the siRNA molecules to increase their stability and their ability to be delivered more efficiently to target cells without increasing their toxicity. This PA is intended to support innovative research in the field of RNAi synthesis and delivery to defined target sites, conducted by small business in partnership with non-profit research institutions (STTR). Examples of projects that this announcement intends to solicit include but are not limited to:

Development and identification of chemical modifications to improve thermal stability of dsRNA, such as LNA (locked nucleic acids) or HNA (hexitol nucleic acids)

Development of nucleic acid modifications, such as 2'-flurobases or 3'-5' phosphoramidate, leading to resistance to nuclease digestion but still allowing efficient processing by Dicer

Identification of chemical modifications leading to preferential strand uptake by RISC, that will enhance specificity and reduce off-target effects

Development of chemical modifications, such as 2,6-diaminopurine (DAP), that enhance base-pairing interactions between the siRNA and targeted mRNA

Development of chemical modifications that will allow or regulate distribution to target tissues, such as to and across the blood-brain-barrier

Identification of chemical modifications, such as phosphorothioate linkages that will enhance the pharmacokinetic properties of siRNA

Development of improved instrumentation that will synthesize long oligonucleotides reliably and with high fidelity

Development of systems for conditional expression of siRNAs

The NIBIB has specific interest in the development of new delivery vehicles for RNAi molecules. Applicants are encouraged to contact program staff regarding the relevance of prospective proposals to the NIBIB.

This funding opportunity will use the STTR (R41/R42) grant mechanisms. Applications may be submitted for support as Phase I, Phase II or Fast-Track grants as described in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF). A parallel funding opportunity announcement of identical scientific scope (PA-06-003) utilizes the Small Business Innovation Research (SBIR) grant mechanism. Applicants may not submit simultaneously identical/essentially identical applications under both this funding opportunity and another HHS FOA, including the SBIR or STTR Parent FOAs (see Small Business Funding Opportunities web page).

Phase II applications in response to this funding opportunity will only be accepted as competing renewals (formerly “competing continuations”) of previously funded Phase I SBIR awards. The Phase II must be a logical extension of the Phase I research but not necessarily as a Phase I project supported in response to this funding opportunity.

The applicant SBC will be solely responsible for planning, directing, and executing the proposed project. Future unsolicited, competing renewal applications based on this project will compete with all STTR applications and will be reviewed according to the customary peer review procedures. Applications that are not funded in the competition described in this FOA may be submitted as RESUBMISSION applications throughGrants.gov Applyusing the standard NIH STTR receipt dates of April 1, August 1, and December 1 (or January 2, May 1, or September 1 for AIDS and AIDS-related STTR applications).

This funding opportunity uses just-in-time concepts. The modular budget format is no longer accepted for STTR grant applications. Applicants must complete and submit budget requests using the Research and Related budget component found in the application package attached to this announcement in Grants.gov Apply.

2. Funds Available

The SF424 (R&R) Application Guide indicates the statutory guidelines of funding support and project duration periods for STTR Phase I and Phase II awards. For this funding opportunity, budgets up to $100,000 total costs per year and time periods up to 2 years for Phase I may be requested. Budgets up to $500,000 total costs per year and up to3years may be requested for Phase II. Total costs include direct costs, F&A, and fee/profit.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

Only United States small business concerns (SBCs) are eligible to submit STTR applications. A small business concern is one that, at the time of award, for both Phase I and Phase II awards, meets all of the following criteria:

1. Is independently owned and operated, is not dominant in the field of operation in which it is proposing, has a place of business in the United States and operates primarily within the United States or makes a significant contribution to the US economy, and is organized for profit.

2. Is at least 51% owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States.

3. Has, including its affiliates, an average number of employees for the preceding 12 months not exceeding 500, and meets the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns are generally considered to be affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both.

Control can be exercised through common ownership, common management, and contractual relationships. The term "affiliates" is defined in greater detail in 13 C.F.R. 121.103. The term "number of employees" is defined in 13 C.F.R. 121.106.

A business concern may be in the form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust, or cooperative. Further information may be obtained athttp://sba.gov/size, or by contacting the Small Business Administration's (SBA) Government Contracting Area Office or Office of Size Standards. One of the circumstances that would lead to a finding that an organization is controlling or has the power to control another organization involves sharing common office space and/or employees and/or other facilities (e.g., laboratory space). Access to special facilities or equipment in another organization is permitted (as in cases where the awardee organization has entered into a subcontractual agreement with another organization for a specific, limited portion of the research project). However, research space occupied by an STTR awardee organization must be space that is available to and under the control of the STTR awardee for the conduct of its portion of the proposed project.

Title 13 C.F.R. 121.3 also states that control or the power to control exists when “key employees of one concern organize a new concern ... and serve as its officers, directors, principal stockholders, and/or key employees, and one concern is furnishing or will furnish the other concern with subcontracts, financial or technical assistance, and/or other facilities, whether for a fee or otherwise.” Where there is indication of sharing of common employees, a determination will be made on a case-by-case basis of whether such sharing constitutes control or the power to control.

For purposes of the STTR program, personnel obtained through a Professional Employer Organization or other similar personnel leasing company may be considered employees of the awardee. This is consistent with SBA’s size regulations, 13C.F.R. 121.106 – Small Business Size Regulations.

All STTR grant applications will be examined with the above eligibility considerations in mind. If it appears that an applicant organization does not meet the eligibility requirements, NIH will request a size determination by the SBA. If eligibility is unclear, NIH will not make an STTR award until the SBA provides a determination.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

For a STTR application, the Project Director/Principal Investigator (PD/PI) may be employed with the SBC or the participating non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC.

The PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration. In all cases, however, the PD/PI’s official relationship with the grantee must entail sufficient opportunity for the PD/PI to carry out his or her responsibilities for the overall scientific and technical direction of the project. Documentation (e.g., consultant, consortium and contractual arrangements) describing the official relationship of the PD/PI with the applicant small business concern should NOT be submitted with the grant application, but a copy must be furnished upon the request of the NIH awarding component.

The following are examples of situations describing the official relationship of the PD/PI with the applicant small business organization:

PD/PI with a full-time, university appointment may also have appointments with other organizations (with or without salary) and still appropriately consider his or her commitment to the university to be “full-time,” consistent with the personnel policies and procedures of the university applied on a routine basis. The PD/PI’s commitment to the university and other organizations (including the applicant small business concern) cannot exceed 100% of his or her total professional effort.

PD/PI with a full-time, 12-month appointment with a small business concern would be considered to have a commitment to the applicant organization of 100% of his or her total professional effort.

PD/PI who has a part-time appointment with a small business concern and has concurrent commitments or appointments with organizations in addition to the small business concern would deem each commitment as a portion of 100% of his or her total professional effort.

In STTR Phase I and Phase II, at least 40% of the work must be performed by the small business concern and at least 30% of the work must be performed by the single, “partnering” research institution. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct and F&A/indirect costs attributable to each party, unless otherwise described and justified in the “Contractual Arrangements” portion of the Research Plan section of the application.

The NIH will accept as many "different" applications as the applicant organization chooses. However, the NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process or service that, with non-substantive modifications, can be applied to a variety of purposes. Likewise, identical or essentially identical grant applications submitted by different applicant organizations will not be accepted. Applicants may not submit simultaneously identical/essentially identical applications under both this funding opportunity and another HHS FOA, including the SBIR or STTR Parent FOAs (see Small Business Funding Opportunities web page).

Section IV. Application and Submission Information

Registration and Instructions for Submission via Grants.gov

To download an Application Package and Instructions for completing the SF424 Research and Related (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that site.

Several of the steps of the registration process could take up to two weeks. Therefore, applicants should immediately check with their business official to determine whether their small business is already registered in both Grants.gov and the Commons.

Note: The STTR applicant organization must officially affiliate the PD/PI with the small business concern in the Commons if the PD/PI is not an employee of the small business concern.

Following are the steps to affiliate a PD/PI to the applicant organization/institution:

1) PD/PI gives Commons user ID and email address to the administrator of the applicant institution. (The email address must be the one that is contained in the Personal Profile for the PD/PI.)

2) Administrator logs into the Commons. (The administrator can be the Signing Official, Administrative Official, or the Accounts Administrator.)

Note: The account cannot have any other roles attached to it other than the PD/PI.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and instructions for this FOA through the Grants.gov Apply http://www.grants.gov/Apply Web site.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all STTR applications using the using the SF424 (R&R) application forms and SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) instructions.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this announcement in Grants.gov APPLY will include all applicable components, required and optional. A completed application in response to this announcement will include the following components:

3.A.1. Letter of Intent A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronicallyPAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted to Grants.gov on or after November 7, 2005 (i.e., the Open Date on Grants.gov) and must be submitted no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission date described above (Section IV.3.A.). If an application is not submitted by that date, the application may be delayed in the review process or not reviewed.

Upon receipt, applications will be transferred from Grants.gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the Signing Official for the organization must verify the submission via Commons within 2 business days of notification of the NIH validation.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review (CSR), NIH. Incomplete applications will not be reviewed.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

All application instructions outlined in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) are to be followed, with the following requirements.

STTR Phase I applications:

Although preliminary data are not required, they may be included.

Items 2-5 of the Research Plan component may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts.

“Introduction” (required for a resubmission application) is limited to one page.

The Biographical Sketch is limited to a maximum of 4 pages for each senior/key person. (This includes the table at the top of the first page.)

There is no further limitation on the total number of pages for the entire Phase I application; however, applicants are encouraged to be succinct.

STTR Phase II applications:

Items 2-5 of the Research Plan component may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts.

“Introduction” (required for a resubmission application) is limited to one page.

The Biographical Sketch is limited to a maximum of 4 pages for each senior/key person. (This includes the table at the top of the first page)

The Phase II application must present a Commercialization Plan (maximum 15 pages) that addresses specific points as described in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) and the SBIR/STTR Information Component.

There is no further limitation on the total number of pages for the entire Phase II application; however, applicants are encouraged to be succinct.

STTR Fast-Track applications

Unlike in the past where Fast-Track applicants were required to submit two separate applications (one for Phase I and one for Phase II), the NIH Fast-Track application is now a single application consisting of Phase I and Phase II activities. See the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF).

The Phase I portion of a Fast-Track must specify clear, measurable goals (milestones) that should be achieved prior to initiating Phase II work.

The Fast-Track application must present a Commercialization Plan (maximum 15 pages) that addresses specific points as described in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) and the SBIR/STTR Information Component.

“Introduction” (required for a resubmission application) is limited to three (3) pages.

Items 2-5 of the Research Plan may not exceed 25 pages. That is, items 2-5 of the Research Plan may not exceed 25 pages. That is, the combined Phase I and Phase II plans for a Fast-track application (for items 2-5) must be contained within the 25-page limit.

Plan for Sharing Research Data

Applicants requesting $500,000 or more in direct costs in any year should include a brief one paragraph description of how final research data will be shared, or explain why data-sharing is not possible. The specific nature of the data to be collected will determine whether or not the final dataset may be shared. If the final data are not amenable to sharing, for example, if they are proprietary, this must be explained in the application. The Small Business Act requires NIH to protect from disclosure and nongovernmental use all SBIR and STTR data developed from work performed under an SBIR and STTR funding agreement for a period of 4 years after the closeout of either a Phase I or Phase II grant unless NIH obtains permission from the awardee to disclose these data. The data rights protection period lapses only upon expiration of the protection period applicable to the SBIR and STTR award, or by agreement between the small business concern and NIH. Applicants are encouraged to discuss their data-sharing plan with the Institute/Center staff likely to accept assignment of their application.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. CriteriaOnly the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the Institutes/Centers (ICs) on the basis of established PHS referral guidelines.

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.

Receive a written critique

Receive a second level of review by an appropriate national advisory council or board.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended SBIR and STTR applications. The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review

Availability of funds

Relevance to program priorities

The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of these criteria in assigning the application's overall score, weighting them as appropriate for each application.

Significance

Approach

Innovation

Investigator

Environment

Additional Review Criteria

The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score.

All STTR Applications

Significance: Does the proposed project have commercial potential to lead to a marketable product, process or service? Does this study address an important problem? What may be the anticipated commercial and societal benefits that may be derived from the proposed research? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the application lead to enabling technologies (e.g., instrumentation, software) for further discoveries? Will the technology have a competitive advantage over existing/alternate technologies that can meet the market needs?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Is the proposed plan a sound approach for establishing technical and commercial feasibility? Does the applicant acknowledge potential problem areas and consider alternative strategies? Are the milestones and evaluation procedures appropriate?

Innovation: Are the aims original and innovative? Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigator: Is the PD/PI appropriately trained and capable of coordinating and managing the proposed STTR? Are the investigators well suited to carry out this work? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Is the work proposed appropriate to the experience level of the PD/PI and other researchers, including consultants and subcontractors (if any)? Are the relationships of the key personnel to the small business and to other institutions appropriate for the work proposed?

Environment: Is there sufficient access to resources (e.g., equipment, facilities)? Does the scientific and technological environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Phase II ApplicationsIn addition to the above review criteria:

1. How well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

2. Did the applicant submit a concise Commercialization Plan that adequately addresses the specific areas described in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) and the SBIR/STTR Information Component?

3. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan?

Resubmission Applications(formerly “amended” applications)In addition to the above criteria, the following criteria will be applied to resubmission applications.

1. Are the responses to comments from the previous SRG review adequate?

1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. Did the applicant submit a concise Commercialization Plan that adequately addresses the specific areas described in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) and the SBIR/STTR Information Component?

3. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

4. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan?

Phase I and Phase II Fast-Track applications that satisfy all of the review criteria will receive a single rating.Failure to provide clear, measurable goals may be sufficient reason for the scientific review group to exclude the Phase II application from Fast-Track review. Items 2-5 of the Research Plan may not exceed 25 pages. That is, the combined Phase I and Phase II plans for a Fast-track application (for items 2-5) must be contained within the 25-page limit.

For Fast-Track applications, the Phase II portion may not be funded until a Phase I final report and other documents necessary for continuation have been received and assessed by program staff that the Phase I milestones have been successfully achieved.

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See item 6 of the Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See item 7 of the Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF424 (R&R) will be assessed.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the percent effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

Period of Support: The appropriateness of the requested period of support in relation to the proposed research. 2.C. Sharing Research Data

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not Applicable

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

Human Subjects Protection:Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

Required Education on the Protection of Human Subject Participants:NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

Standards for Privacy of Individually Identifiable Health Information:The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR Website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.